Effect of Physalis angulata leaf extract cream on Interleukin-4, Interleukin-6, and Immunoglobulin-E in mice with induced atopic dermatitis

Main Article Content

Dhany Prafita Ekasari
Santosa Basuki
Wuriandaru Kurniasih
Herwinda Brahmanti
Aunur Rofiq


The prevalence of atopic dermatitis (AD) and allergic or irritant contact dermatitis has been increasing significantly in the general population. Interleukin- 4 (IL-4), interleukin-6 (IL-6), and immunoglobulin E (IgE) play a key role in the pathogenesis of AD. Physalis angulata (PA) leaves reportedly have anti-inflammatory effects by impeding IL-4, IL-6, and IgE. This study aimed to evaluate the effect of PA leaf extract cream on IL-4, IL-6, and IgE using 2,4-dinitrochlorobenzene (DNCB) to induce AD-like skin inflammation in a mice model.

This study used an experimental design involving 30 BALB/c mice, that were randomized into 3 groups: 1) control group receiving no treatment; 2) Vehicle treatment group receiving vehicle cream preparation; 3) PA treatment group receiving 10% PA leaf extract cream after induction of AD-like skin inflammation by DNCB. After 30 days, tissue samples were extracted from the skin lesions to measure IL-4 and IL-6 levels, and serum to measure IgE using ELISA. One-way Anova, Kruskal-Wallis and Mann-Whitney tests were used to analyze the data.

Group 3 (PA treatment) had significantly lower IL-4 (281.15 ± 43.14 pg/mL) than group 2 (vehicle cream treatment) (388.89±135.88 pg/ml) (p=0.001). However, although IL-6 and IgE levels were lower in group 3 than in group 2, the differences were statistically not significant (p=0.096 and p=0.479 respectively).

There were lower levels of IL-4, IL-6, and IgE in the group receiving PA leaf extract cream than in the group receiving vehicle cream preparation. Therefore, PA leaf extract cream may have therapeutic potential in AD.

Article Details

How to Cite
Ekasari, D. P. ., Basuki, S. ., Kurniasih, W., Brahmanti, H. ., & Rofiq, A. . (2023). Effect of Physalis angulata leaf extract cream on Interleukin-4, Interleukin-6, and Immunoglobulin-E in mice with induced atopic dermatitis. Universa Medicina, 42(2), 150–159. https://doi.org/10.18051/UnivMed.2023.v42.150-159
Original Articles


Peng W, Novak N. Pathogenesis of atopic dermatitis. Clin Exp Allergy 2015;45:566-74. doi: 10.1111/cea.12495.

Hur SS, Choi SW, Lee DR, Park JH, Chung TH. Advanced effect of Moringa oleifera bioconversion by Rhizopus oligosporus on the treatment of atopic dermatitis: preliminary study. Evid Based Complement Alternat Med 2018;2018: 7827565. doi: 10.1155/2018/7827565.

Lim JM, Lee B, Min JH, et al. Effect of peiminine on DNCB-induced atopic dermatitis by inhibiting inflammatory cytokine expression in vivo and in vitro. Int Immunopharmacol 2018;56:135-42. doi: 10.1016/j.intimp.2018.01.025.

Rodrigues MA, Torres T. JAK/STAT inhibitors for the treatment of atopic dermatitis. J Dermatolog Treat 2019;31:33-40. doi: 10.1080/09546634. 2019.1577549.

Simpson EL, Leung DYM, Eichenfield LF, Boguniewicz M. Atopic dermatitis: In: Kang S, Amagai M, Bruckner Al et al., editors. Fitzpatrick’s dermatology in general medicine, 9th ed. New York: McGraw Hill; 2019. p.363-84.

Bao L, Shi VY, Chan LS. IL-4 up-regulates epidermal chemotactic, angiogenic, and pro-inflammatory genes and down-regulates antimicrobial genes in vivo and in vitro: relevant in the pathogenesis of atopic dermatitis. Cytokine 2013;61:419-25. doi: 10.1016/j.cyto.2012.10.031.

Bao L, Zhang H, Chan LS. The involvement of the JAK-STAT signaling pathway in chronic inflammatory skin disease atopic dermatitis. Jak-Stat 2013;2:24137. doi: 10.4161/jkst.24137.

Sroka-Tomaszewska J, Trzeciak M. Molecular mechanisms of atopic dermatitis pathogenesis. Int J Mol Sci 2021;22:4130. doi: 10.3390/ijms22084130.

Jang S, Ohn J, Kim JW et al. Caffeoyl–Pro–His amide relieve DNCB-induced atopic dermatitis-like phenotypes in BALB/c mice. Sci Rep 2020; 10:1-9. doi: 10.1038/s41598-020-65502-2.

Karuppagounder V, Arumugam S, Thandavarayan RA, Sreedhar R, Giridharan VV, Watanabe K. Molecular targets of quercetin with anti-inflammatory properties in atopic dermatitis. Drug Discovery Today 2016;21:632-9. doi: 10.1016/j.drudis.2016.02.011.

Lee DE, Clark AK, Tran KA, Shi VY. New and emerging targeted systemic therapies: a new era for atopic dermatitis. J Dermatolog Treat 2018;29: 364-74. doi: 10.1080/09546634.2017.1373736.

Nguyen KNH, Kim KH. Determination of phenolic acids and flavonoids in leaves, calyces, and fruits of Physalis angulata L. in Viet Nam. Pharmacia 2021;68:501-09. doi:10.3897/pharmacia.68.e66044.

Yang YJ, Yi L, Wang Q, Xie BB, Dong Y, Sha CW. Anti-inflammatory effects of physalin E from Physalis angulata on lipopolysaccharide-stimulated RAW 264.7 cells through inhibition of NF-êB pathway. Immunopharmacol Immunotoxicol 2017;39:74-9. doi: 10.1080/08923973.2017.1282514.

Pereda MDCV, Dieamant G, Nogueira C, et al. Sterol standardized phytopharmaceutical from ground cherry: Corticoid like properties on human keratinocytes and fibroblasts and its effects in a randomized double blind placebo controlled clinical trial. J Cosmet Dermatol 2018;00:1-13. doi: 10.1111/jocd.12851.

Pinto NB, Morais TC, Carvalho KMB, et al. Topical anti-inflammatory potential of physalin E from Physalis angulata on experimental dermatitis in mice. Phytomedicine 2010;17:740-3. doi: 10.1016/j.phymed.2010.01.006.

Herdiana Y, Susilo H, Muztabadihardja. Formulasi krim pencerah wajah ekstrak etanol 70% daun ciplukan (Physalis angulata L. [thesis]. Program Studi Farmasi FMIPA, Universitas Pakuan Bogor; 2014.

Abdul-Nasir-Deen AY, Boakye YD, Osafo N, et al. Anti-inflammatory and wound healing properties of methanol leaf extract of Physalis angulata L. South African J Botany 2020;133:124-31. doi: 10.1016/j.sajb.2020.06.030.

Hamad AF, Han JH, Rather IA. Mouse model of DNCB-induced atopic dermatitis. Bangladesh J Pharmac 2017;12:147-50. doi: 10.3329/bjp.v12i2. 31950.

Serafini MR, Detoni CB, Menezes PD, et al. UVA-UVB photoprotective activity of topical formulations containing Morinda citrifolia extract. BioMed Res Int 2014. doi: 10.1155/2014/587819.

Hou DD, Zhang W, Gao YL, et al. Anti-inflammatory effects of quercetin in a mouse model of MC903-induced atopic dermatitis. Int Immunopharmacol 2019;74:105676. doi: 10.1016/j.intimp.2019.105676.

Iswahyudi I. Analisis fitokimia dan profil kromatografi lapis tipis ekstrak etanol daun ciplukan (Physalis angulata l.) dengan berbagai metode pengeringan simplisia. J Mahasiswa Farmasi Fakultas Kedokteran UNTAN 2015;3.

Mastuti R, Rosyidah M. Diversity of bioactive secondary metabolites produced by medicinal plants of Physalis angulata L. (Ciplukan). IOP Conf. Ser.: Earth Environ Sci 743:012081. doi: 10.1088/1755-1315/743/1/012081.

Mastuti R, Batoro J, Waluyo B. Pengaruh elisitor kitosan terhadap kandungan withanolid tunas in vitro aksesi tanaman Physalis angulata dari Pulau Madura. J Tumbuhan Obat Indonesia 2021;14:1-4. doi: 10.22435/jtoi.v14i1.43011.

Akomolafe SA, Oyeleye SI, Olasehinde TA, Oboh G. Phenolic characterization, antioxidant activities, and inhibitory effects of Physalis angulata and Newbouldia laevis on enzymes linked to erectile dysfunction. Int J Food Properties. 2018;21:645-54. doi: 10.1080/10942912.2018.1446149.

Furue M, Ulzii D, Vu YH, Tsuji G, Kido-Nakahara M, Nakahara T. Atopic Dermatitis and type 2 immune deviation . Curr Treat Options Allergy 2019;6:200-10. doi: 10.1007/s40521-019-00219-w.

Huet F, Severino-Freire M, Chéret J, et al. Reconstructed human epidermis for in vitro studies on atopic dermatitis: a review. J Dermatol Sci 2018;89:213-8. doi: 10.1016/j.jdermsci.2017. 11.015.

Munera-Campos M, Carrascosa JM. Innovation in atopic dermatitis: from pathogenesis to treatment. Actas Dermosifiliogr (English Edition) 2020;111:205-21. doi:10.1016/j.adengl.2020.03.001.

Wang L, Xian YF, Hu Z, et al. Efficacy and action mechanisms of a Chinese herbal formula on experimental models of atopic dermatitis. J Ethnopharmacol 2021;274:114021. doi: 10.1016/j.jep.2021.114021.

Giménez Arnau AM, Ribas Llauradó C, Mohammad Porras N, Deza G, Pujol RM, Gimeno R. IgE and high affinity IgE receptor in chronic inducible urticaria, pathogenic, and management relevance. Clin Transl Allergy 2022;e12117. https://doi.org/10.1002/clt2.121171.

Èepelak I, Dodig S, Paviæ I. Filaggrin and atopic march. Biochem Med (Zagreb) 2019;29:214-27. doi: 10.11613/BM.2019.020501.

Weidinger S, Beck LA, Bieber T, Kabashima K, Irvine AD. Atopic dermatitis. Nat Rev Dis Primers 2018;4:1. doi: 10.1038/s41572-018-0001-z.

Kim JE, Kim JS, Cho DH, Park HJ. Molecular mechanisms of cutaneous inflammatory disorder: atopic dermatitis. Int J Mol Sci 2016;17:1234. doi: 10.3390/ijms17081234.

Rerknimitr P, Otsuka A, Nakashima C, Kabashima K. The etiopathogenesis of atopic dermatitis: barrier disruption, immunological derangement, and pruritus. Inflamm Regen 2017;37:1-5. doi: 10.1186/s41232-017-0044-7.

Silverberg JI, Kantor R. The role of interleukins 4 and/or 13 in the pathophysiology and treatment of atopic dermatitis. Dermatol Clin 2017;35:327-34. doi: 10.1016/j.det.2017.02.005.

Wu S, Pang Y, He Y, et al. A comprehensive review of natural products against atopic dermatitis: Flavonoids, alkaloids, terpenes, glycosides and other compounds. Biomed Pharmacother 2021; 140:111741. doi:10.1016/j.biopha.2021.111741.

Karuppagounder V, Arumugam S, Thandavarayan RA, et al. Modulation of HMGB 1 translocation and RAGE/NFêB cascade by quercetin treatment mitigates atopic dermatitis in NC/Nga transgenic mice. Exp Dermatol 2015;24:418-23. doi: 10.1111/exd.12685.

Park EJ, Kim JY, Jeong MS, et al. Effect of topical application of quercetin-3-O-(2 3 -gallate)-á-l-rhamnopyranoside on atopic dermatitis in NC/Nga mice. J Dermatol Sci 2015;77:166-72. doi: 10.1016/j.jdermsci.2014.12.005.